scholarly journals Differential Transcriptomic Profiles in Canine Intestinal Organoids Following Lipopolysaccharide Stimulation

2022 ◽  
Author(s):  
Dipak K. Sahoo ◽  
Dana C. Borcherding ◽  
Lawrance Chandra ◽  
Albert E. Jergens ◽  
Todd Atherly ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cancer Progression ◽  
Intestinal Inflammation ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Signal Transduction Pathway ◽  
Glutathione Metabolism ◽  
Study Objective ◽  
Altered Expression ◽  
Chronic Intestinal Inflammation

Abstract Lipopolysaccharide (LPS) is associated with chronic intestinal inflammation and promotes intestinal cancer progression in the gut. While the interplay between LPS and intestinal immune cells has been well characterized, little is known about LPS and intestinal epithelium interactions. In this study, we explored the differential effect of LPS on proliferation and the transcriptome in 3D enteroids/colonoids obtained from dogs with naturally occurring gastrointestinal (GI) diseases, such as Inflammatory Bowel Disease (IBD) and GI mast cell tumor. The study objective was to analyze LPS-induced modulation of signaling pathways involving the intestinal epithelia and critical to colorectal cancer development in the context of IBD or a tumor microenvironment. While LPS incubation resulted in a pro-cancer gene expression pattern and stimulated proliferation of IBD enteroids and colonoids, down-regulation of several cancer-associated genes like CRYZL1, Gpatch4, SLC7A1, ATP13A2, and ZNF358 was also observed in tumor enteroids. Genes participating in porphyrin metabolism (CP), thiamine and purine metabolism (TAP2, EEF1A1), arachidonic acid, and glutathione metabolism (GPX1) exhibited a similar pattern of altered expression between IBD enteroids and IBD colonoids following LPS stimulation. In contrast, genes involved in anion transport, transcription and translation, apoptotic processes, and regulation of adaptive immune responses showed opposite expression patterns between IBD enteroids and colonoids following LPS treatment. In brief, the cross-talk between LPS/TLR4 signal transduction pathway and several metabolic pathways, such as fatty acid degradation and biosynthesis, and purine, thiamine, arachidonic acid, and glutathione metabolism, may be important in driving chronic intestinal inflammation and intestinal carcinogenesis.

scholarly journals The Mechanobiome: A Goldmine for Cancer Therapeutics

2020 ◽  
Author(s):  
Eleana Parajón ◽  
Alexandra Surcel ◽  
Douglas N. Robinson
Keyword(s):  
Cancer Progression ◽  
Expression Patterns ◽  
Cancer Therapeutics ◽  
Cellular Systems ◽  
Cancer Drug ◽  
Altered Expression ◽  
Mechanical Adaptation ◽  
Gene And Protein Expression ◽  
Wide Range ◽  
Cancer Types

Cancer progression is dependent on heightened mechanical adaptation, both for the cells' ability to change shape and to interact with varying mechanical environments. This type of adaptation is dependent on mechanoresponsive proteins that sense and respond to mechanical stress, as well as their regulators. Mechanoresponsive proteins are part of the mechanobiome, which is the larger network that constitutes the cell's mechanical systems that are also highly integrated with many other cellular systems, such as gene expression, metabolism, and signaling. Despite the altered expression patterns of key mechanobiome proteins across many different cancer types, pharmaceutical targeting of these proteins has been overlooked. Here we review the biochemistry of key mechanoresponsive proteins, specifically nonmuscle myosin II, α-actinins, and filamins, as well as the partnering proteins 14-3-3 and CLP36. We also examined a wide range of data sets to assess how gene and protein expression levels of these proteins are altered across many different cancer types. Finally, we determined the potential of targeting these proteins to mitigate invasion or metastasis and suggest that the mechanobiome is a goldmine of opportunity for anti-cancer drug discovery and development.

scholarly journals Microarray Analysis Reveals Characteristic Changes of Host Cell Gene Expression in Response to Attenuated Modified Vaccinia Virus Ankara Infection of Human HeLa Cells

2004 ◽  
Vol 78 (11) ◽  
pp. 5820-5834 ◽  
Author(s):  
Susana Guerra ◽  
Luis A. López-Fernández ◽  
Raquel Conde ◽  
Alberto Pascual-Montano ◽  
Keith Harshman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Immune Modulation ◽  
Expression Patterns ◽  
Family Members ◽  
Signal Transduction Pathway ◽  
Gene Clusters ◽  
Altered Expression ◽  
Modified Vaccinia Virus Ankara

ABSTRACT The potential use of the modified vaccinia virus Ankara (MVA) strain as a live recombinant vector to deliver antigens and elicit protective immune responses against infectious diseases demands a comprehensive understanding of the effect of MVA infection on human host gene expression. We used microarrays containing more than 15,000 human cDNAs to identify gene expression changes in human HeLa cell cultures at 2, 6, and 16 h postinfection. Clustering of the 410 differentially regulated genes identified 11 discrete gene clusters with altered expression patterns after MVA infection. Clusters 1 and 2 (accounting for 16.59% [68 of 410] of the genes) contained 68 transcripts showing a robust induction pattern that was maintained during the course of infection. Changes in cellular gene transcription detected by microarrays after MVA infection were confirmed for selected genes by Northern blot analysis and by real-time reverse transcription-PCR. Upregulated transcripts in clusters 1 and 2 included 20 genes implicated in immune responses, including interleukin 1A (IL-1A), IL-6, IL-7, IL-8, and IL-15 genes. MVA infection also stimulated the expression of NF-κB and components of the NF-κB signal transduction pathway, including p50 and TRAF-interacting protein. A marked increase in the expression of histone family members was also induced during MVA infection. Expression of the Wiskott-Aldrich syndrome family members WAS, WASF1, and the small GTP-binding protein RAC-1, which are involved in actin cytoskeleton reorganization, was enhanced after MVA infection. This study demonstrates that MVA infection triggered the induction of groups of genes, some of which may be involved in host resistance and immune modulation during virus infection.

scholarly journals The Biomarker Potential of Caveolin-1 in Penile Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Andrej Panic ◽  
Henning Reis ◽  
Alina Wittka ◽  
Christopher Darr ◽  
Boris Hadaschik ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Penile Cancer ◽  
Expression Patterns ◽  
Human Papilloma Virus Infection ◽  
Tumor Stroma ◽  
Stromal Compartment ◽  
Altered Expression ◽  
Caveolin 1 ◽  
Clinicopathological Significance ◽  
Cav1 Expression

Various types of human cancers were characterized by an altered expression of epithelial or stromal caveolin-1 (CAV1). However, the clinical significance of CAV1 expression in penile cancer remains largely unknown. Here the expression patterns of CAV1 were analyzed in a retrospective cohort (n=43) of penile squamous cell carcinomas (SCC). Upon penile cancer progression, significantly increased CAV1-levels were determined within the malignant epithelium, whereas within the tumor stroma, namely the fibroblastic tumor compartment harboring activated and/or cancer associated fibroblasts, CAV1 levels significantly decline. Concerning the clinicopathological significance of CAV1 expression in penile cancer as well as respective epithelial-stromal CAV1 distributions, high expression within the tumor cells as well as low expression of CAV1 within the stromal compartment were correlated with decreased overall survival of penile cancer patients. Herein, CAV1 expressions and distributions at advanced penile cancer stages were independent of the immunohistochemically proven tumor protein p53 status. In contrast, less differentiated p16-positive tumor epithelia (indicative for human papilloma virus infection) were characterized by significantly decreased CAV1 levels. Conclusively, we provide further and new evidence that the characteristic shift in stromal‐epithelial CAV1 being functionally relevant to tumor progression even occurs in penile SCC.

scholarly journals Experimental Stroke Induces Chronic Gut Dysbiosis and Neuroinflammation in Male Mice

2020 ◽  
Author(s):  
Allison L. Brichacek ◽  
Divine C. Nwafor ◽  
Stanley A. Benkovic ◽  
Sreeparna Chakraborty ◽  
Sophia M. Kenney ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Experimental Stroke ◽  
List Type ◽  
Study Objective ◽  
Post Stroke ◽  
Gut Dysbiosis ◽  
Intestinal Pathology ◽  
Chronic Intestinal Inflammation

AbstractRecent literature implicates gut epithelia mucosa and intestinal microbiota as important players in post-stroke morbidity and mortality. As most studies have focused on the acute effects of stroke on gut dysbiosis, our study objective was to measure chronic, longitudinal changes in the gut microbiota and intestinal pathology following ischemic stroke. We hypothesized that mice with experimental ischemic stroke would exhibit chronic gut dysbiosis and intestinal pathology up to 36 days post-stroke compared to sham controls. Male C57BL/6J mice were subjected to 60 minutes of transient middle cerebral artery occlusion (tMCAO) or sham surgery. To determine the long-term effects of tMCAO on gut dysbiosis, fecal boli were collected pre- and post-tMCAO on days 0, 3, 14, and 28. Bioinformatics analysis demonstrate significant differences in abundance among Firmicutes and Bacteroidetes taxa at the phylum, family, and species levels in tMCAO compared to sham mice that persisted up to one month post-stroke. The most persistent changes in post-stroke microbial abundance were a decrease in bacteria family S24-7 and significant increases in Ruminococcaceae. Overall, these changes resulted in a persistently increased Firmicutes:Bacteroidetes ratio in stroke animals. Intestinal histopathology showed evidence of chronic intestinal inflammation that included marked increases in immune cell infiltration with mild-moderate epithelial hyperplasia and villous blunting. Increased astrocyte and microglial activity were also detected one-month post-stroke. These results demonstrate that acute, post-stroke disruption of the gut-brain-microbiota axis progresses to chronic gut dysbiosis, intestinal inflammation, and chronic neuroinflammation.Clinical PerspectivesThe microbiota-gut-brain axis, recently implicated in several neurological disorders, remains largely unexplored at chronic time points post-tMCAO.Our results demonstrate chronic gut dysbiosis, prolonged behavioral deficits, and persistent cerebral and intestinal inflammation post-tMCAO in male C57BL/6J mice.These results suggest that manipulation of microbiota may help reduce poor outcomes after stroke and lead to improved post-stroke functional recovery.

Role of CD5 expression on TCRγδ T cell-differentiation and development of chronic intestinal inflammation

2001 ◽  
Vol 120 (5) ◽  
pp. A517-A517
Author(s):  
A MIZOGUCHI ◽  
E MIZOGUCHI ◽  
Y DEJONG ◽  
H TAKEDATSU ◽  
F PREFFER ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Intestinal Inflammation ◽  
T Cell Differentiation ◽  
Chronic Intestinal Inflammation

scholarly journals Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2602
Author(s):  
Emilie Viennois ◽  
Benoit Chassaing
Keyword(s):  
Intestinal Inflammation ◽  
Tumor Development ◽  
Low Grade ◽  
Gastrointestinal Cancers ◽  
Cancer Initiation ◽  
And Function ◽  
The Impact ◽  
Chronic Intestinal Inflammation ◽  
Low Grade Inflammation ◽  
Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

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